Competition between ethanol clearance and retinoic acid biosynthesis in the induction of fetal alcohol syndrome

Yehuda Shabtai, Abraham Fainsod*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations

Abstract

Several models have been proposed to explain the neurodevelopmental syndrome induced by exposure of human embryos to alcohol, which is known as fetal alcohol spectrum disorder (FASD). One of the proposed models suggests a competition for the enzymes required for the biosynthesis of retinoic acid. The outcome of such competition is development under conditions of reduced retinoic acid signaling. Retinoic acid is one of the biologically active metabolites of vitamin A (retinol), and regulates numerous embryonic and differentiation processes. The developmental malformations characteristic of FASD resemble those observed in vitamin A deficiency syndrome as well as from inhibition of retinoic acid biosynthesis or signaling in experimental models. There is extensive biochemical and enzymatic overlap between ethanol clearance and retinoic acid biosynthesis. Several lines of evidence suggest that in the embryo, the competition takes place between acetaldehyde and retinaldehyde for the aldehyde dehydrogenase activity available. In adults, this competition also extends to the alcohol dehydrogenase activity. Ethanol-induced developmental defects can be ameliorated by increasing the levels of retinol, retinaldehyde, or retinaldehyde dehydrogenase. Acetaldehyde inhibits the production of retinoic acid by retinaldehyde dehydrogenase, further supporting the competition model. All of the evidence supports the reduction of retinoic acid signaling as the etiological trigger in the induction of FASD.

Original languageAmerican English
Pages (from-to)148-160
Number of pages13
JournalBiochemistry and Cell Biology
Volume96
Issue number2
DOIs
StatePublished - 2018

Bibliographical note

Publisher Copyright:
© 2018 Published by NRC Research Press.

Keywords

  • Alcohol dehydrogenase
  • Embryo development
  • Retinaldehyde dehydrogenase
  • Vitamin A deficiency
  • Vitamin A metabolism

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